It is the purpose of this proposal to explore the participation of bacterial endotoxin in the immunologic perturbations which follow major thermal injuries. With the central hypothesis that endotoxin derived from normal gastrointestinal flora wound-contaminating Gram negative organisms plays a significant immunologic role in the following specific problems will be addressed: 1) Specific endotoxins will be isolated and identified from burn patient sera via column chromatography and chromatofocusing techniques in conjunction with mixed lymphocyte cultures as an assay of immunological activity. 2) The effect of purified endotoxin, and of endotoxin-containing burn sera upon human natural killer cell cytotoxicity will be studied in vitro. 3) Since the Limulus test is currently inadequate for the detection and study of endotoxin in patient sera, we will develop a radioimmunoassay for the general detection of endotoxin. 4) Laboratory indications of bacterial influence upon the immune response will be correlated with clinical events in burn patients via our computer data base, and the value of specific laboratory tests in predicting morbidity and mortality will be evaluated. These studies are primarily direct, human studies, though New Zealand white rabbits will be used in the generation of antibody.